DOCSLIB.ORG

Immune Complexes As Therapy for Autoimmunity

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Immune Complexes As Therapy for Autoimmunity Immune complexes as therapy for autoimmunity Raphael Clynes J Clin Invest. 2005;115(1):25-27. https://doi.org/10.1172/JCI23994. Commentary For several decades, intravenous Ig has been used as treatment for a variety of immune-related diseases, including immune thrombocytopenic purpura (ITP), autoimmune neuropathies, systemic lupus erythematosus, myasthenia gravis, Guillain-Barré syndrome, skin blistering syndromes, and Kawasaki disease. Despite years of use, its mechanism of immunomodulation is still unclear. Recent studies using mouse models of ITP and arthritis, including one reported in this issue of the JCI, now provide some insights into this mechanism and the rationale for the development of Fcγ receptor– targeted therapeutics. Find the latest version: https://jci.me/23994/pdf commentaries this is most welcome, particularly for science that appears to promise so much 4. Studer, L., Tabar, V., and McKay, R.D. 1998. Trans- plantation of expanded mesencephalic precursors investigators working on strategies for cell for the treatment of human diseases. leads to recovery in parkinsonian rats. Nat. Neurosci. replacement the United States, who must 1:290–295. be feeling something of a déjà vu in face Address correspondence to: J. William 5. Isacson, O., et al. 2001. Cell implantation therapies of yet another presidential moratorium, Langston, The Parkinson’s Institute, for Parkinson’s disease using neural stem, trans- genic or xenogeneic donor cells. Parkinsonism Relat. this time limiting the number of human 1170 Morse Avenue, Sunnyvale, Cali- Disord. 7:205–212. stem cell lines that can be used for research fornia 94089-1605, USA. Phone: (408) 6. Sanchez-Pernaute, R., Studer, L., Bankiewicz, K.S., and treatment. Ironically, this frustration 734-2800; Fax: (408) 734-8522; E-mail: Major, E.O., and McKay, R.D. 2001. In vitro genera- tion and transplantation of precursor-derived human recently led California voters to approve [email protected]. dopamine neurons. J. Neurosci. Res. 65:284–288. a $3 billion initiative to fund stem cell 7. Kim, J.H., et al. 2002. Dopamine neurons derived research, which some have predicted will 1. Freed, C.R., et al. 2001. Transplantation of embry- from embryonic stem cells function in an animal lead to a “gold rush” on stem cell research onic dopamine neurons for severe Parkinson’s model of Parkinson’s disease. Nature. 418:50–56. disease. N. Engl. J. Med. 344:710–719. 8. Takagi, Y., et al. 2005. Dopaminergic neurons gen- (9). Regardless of whether or not this 2. Olanow, C.W., et al. 2003. A double-blind con- erated from monkey embryonic stem cells func- proves to be the case, it can be hoped that trolled trial of bilateral fetal nigral transplantation tion in a Parkinson primate model. J. Clin. Invest. this new initiative will serve as a beacon of in Parkinson’s disease. Ann. Neurol. 54:403–414. 115:102–109. doi:10.1172/JCI200521137. 3. Kordower, J.H., and Sortwell, C.E. 2000. Neuro- 9. Holden, C. 2004. U.S. science policy. California’s hope for scientists and patients alike as pathology of fetal nigra transplants for Parkinson’s Proposition 71 launches stem cell gold rush. Sci- we press ahead in this challenging area of disease. Prog. Brain Res. 127:333–344. ence. 306:1111. Immune complexes as therapy for autoimmunity Raphael Clynes Department of Medicine and Microbiology, Columbia University, New York, New York, USA. For several decades, intravenous Ig has been used as treatment for a variety dependent macrophages, whereas the mac- of immune-related diseases, including immune thrombocytopenic purpura rophage responsible for FcγRIII-mediated (ITP), autoimmune neuropathies, systemic lupus erythematosus, myasthe- platelet clearance is CSF-1 independent (8). nia gravis, Guillain-Barré syndrome, skin blistering syndromes, and Kawa- Thus, while other targets may prove effective saki disease. Despite years of use, its mechanism of immunomodulation in the treatment of immune complex–related is still unclear. Recent studies using mouse models of ITP and arthritis, (IC-related) autoimmunity (9, 10), at least 2 including one reported in this issue of the JCI (see the related article begin- distinct FcγR therapeutic approaches are ning on page 155), now provide some insights into this mechanism and the tenable: direct blockade of the phagocytic Fc rationale for the development of Fcγ receptor–targeted therapeutics. receptors and IVIg-triggered, FcγRIIB-medi- ated inhibition (Figure 1). Fc receptors in the pathogenesis tive therapy in ITP. Indeed, this has proven and treatment of ITP to be a valid approach; antibodies that block What is the active component Intravenous Ig (IVIg) is remarkably FcγRIII have been shown to be effective in of IVIg and intravenous anti-D? effective in the treatment of immune murine studies (2, 4) as well as in pilot clini- A related therapeutic, intravenous anti-D, has thrombocytopenic purpura (ITP), with cal studies (5). also been highly effective in ITP, but only in improved platelet counts seen in 80% of Although activating Fc receptor blockade is Rh+ patients. The active component is clearly treated patients. ITP occurs in patients as the an appealing mechanism, a second, unexpect- anti-D antibodies that generate large par- result of the generation of autoantibodies ed FcγR-related pathway is clearly relevant to ticulate ICs, namely opsonized rbcs, in Rh+ that bind to platelet surface antigens. These the therapeutic action of IVIg. It was recently patients. In contrast, the active components opsonized platelets are phagocytosed by shown (4) that the protective effect of IVIg is in IVIg, a product obtained from sera pooled Fc receptor–bearing splenic and hepatic associated with upregulation of the inhibito- from thousands of donors, could conceiv- macrophages (1). In the mouse, macro- ry receptor FcγRIIB on splenic macrophages ably include a variety of Fc receptor–binding phage-mediated clearance occurs via acti- and is abrogated in mice lacking FcγRIIB. ligands. In addition to the dominant species vating Fc receptors, with complement-medi- Curiously, this effect is independent of SHIP of monomeric IgG (which would bind FcRn ated uptake playing little or no role (2, 3). and SHP-1 (6), the 2 downstream inhibi- and the high-affinity FcγRI), multiple types Thus, blockade of activating Fcγ receptors tory phosphatases previously assumed to of ICs, which bind all Fc receptors, are likely (FcγRs) would be predicted to be an effec- be responsible for the inhibitory signaling to form in vivo after the administration of pathway. Redundant functions of SHIP and IVIg. These complexes of varying valencies Nonstandard abbreviations used: FcγR, Fcγ receptor; SHP-1 or other phosphatases downstream include cell-associated and soluble host IC, immune complex; ITP, immune thrombocytopenic of FcγRIIB may be responsible (7), but as yet antigens bound by donor natural antibodies purpura; IVIg, intravenous Ig. the FcγRIIB-mediated signal is unclear. Add- as well as dimers and aggregated Igs formed Conflict of interest: The author has declared that no conflict of interest exists. ing further to the mystery is the observation in the IVIg product itself. Using mimetic Citation for this article: J. Clin. Invest. 115:25–27 that 2 distinct macrophage populations are modeling studies, Siragam et al. (11) suggest (2005). doi:10.1172/JCI200523994. involved; IVIg protection requires CSF-1– that the 2 therapeutics IVIg and anti-D have The Journal of Clinical Investigation http://www.jci.org Volume 115 Number 1 January 2005 25 commentaries Targeting FcγRIIB directly by cross-linking FcγRIIB-specific antibodies has been shown to be beneficial in the mouse model of ITP, and injection of small, preformed ICs is also protective (18). The current work provides another potential solution, namely injection of antibodies with specificities for serum proteins including albumin and transferrin, which provide FcγRII-dependent protection (11). Monoclonal antibodies recognizing a single epitope form monomeric ICs, imply- ing that clustering of FcγRs by these small ICs is not required for their therapeutic effect. Even with polyclonal α-albumin or α-transferrin antibodies, the resultant ICs formed in vivo are still likely to be quite small, since the serum target proteins are present in such large molar excess. While this is an intriguing approach, an obvious concern is the potential for untoward IC- triggered hypersensitivity responses, which might complicate its clinical use. Implications for other autoimmune states Siragam et al. extend their observa- tions beyond antibody-mediated thrombocytopenia in showing that both IVIg and its mimetic anti-murine albumin antibodies protect in the K/BxN serum– induced arthritis model (11). The clinical Figure 1 benefit of IVIg has been spotty in autoim- Inhibition of phagocytosis in vivo can be accomplished via IC-mediated inhibition of FcγR func- tional activity. These complexes, varying in size and valency, operate through distinct mechanis- mune conditions, such as rheumatoid tic pathways. IVIg leads to the formation of variably sized ICs, including small monomeric and arthritis (19–24), in which autoaggressive T dimeric complexes. The small ICs (Ig dimers or soluble antigen/donor Ig complexes) require cells are believed to be the culprits. Recent CSF-1–dependent macrophages and FcγRII expression to mediate their as-yet-undefined anti- attention in these T cell–mediated diseases, inflammatory effect. Intravenous anti-D generates large particulate ICs, namely opsonized rbcs.
Load more

Recommended publications
  • Primary Sjogren Syndrome: Focus on Innate Immune Cells and Inflammation
    Review Primary Sjogren Syndrome: Focus on Innate Immune Cells and Inflammation Chiara Rizzo 1, Giulia Grasso 1, Giulia Maria Destro Castaniti 1, Francesco Ciccia 2 and Giuliana Guggino 1,* 1 Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Rheumatology Section, University of Palermo, Piazza delle Cliniche 2, 90110 Palermo, Italy; [email protected] (C.R.); [email protected] (G.G.); [email protected] (G.M.D.C.) 2 Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Via L. De Crecchio 7, 80138 Naples, Italy; [email protected] * Correspondence: [email protected]; Tel.: +39-091-6552260 Received: 30 April 2020; Accepted: 29 May 2020; Published: 3 June 2020 Abstract: Primary Sjogren Syndrome (pSS) is a complex, multifactorial rheumatic disease that mainly targets salivary and lacrimal glands, inducing epithelitis. The cause behind the autoimmunity outbreak in pSS is still elusive; however, it seems related to an aberrant reaction to exogenous triggers such as viruses, combined with individual genetic pre-disposition. For a long time, autoantibodies were considered as the hallmarks of this disease; however, more recently the complex interplay between innate and adaptive immunity as well as the consequent inflammatory process have emerged as the main mechanisms of pSS pathogenesis. The present review will focus on innate cells and on the principal mechanisms of inflammation connected. In the first part, an overview of innate cells involved in pSS pathogenesis is provided, stressing in particular the role of Innate Lymphoid Cells (ILCs). Subsequently we have highlighted the main inflammatory pathways, including intra- and extra-cellular players.
    [Show full text]
  • Autoimmunity and Organ Damage in Systemic Lupus Erythematosus
    REVIEW ARTICLE https://doi.org/10.1038/s41590-020-0677-6 Autoimmunity and organ damage in systemic lupus erythematosus George C. Tsokos ✉ Impressive progress has been made over the last several years toward understanding how almost every aspect of the immune sys- tem contributes to the expression of systemic autoimmunity. In parallel, studies have shed light on the mechanisms that contribute to organ inflammation and damage. New approaches that address the complicated interaction between genetic variants, epigen- etic processes, sex and the environment promise to enlighten the multitude of pathways that lead to what is clinically defined as systemic lupus erythematosus. It is expected that each patient owns a unique ‘interactome’, which will dictate specific treatment. t took almost 100 years to realize that lupus erythematosus, strongly to the heterogeneity of the disease. Several genes linked to which was initially thought to be a skin entity, is a systemic the immune response are regulated through long-distance chroma- Idisease that spares no organ and that an aberrant autoimmune tin interactions10,11. Studies addressing long-distance interactions response is involved in its pathogenesis. The involvement of vital between gene variants in SLE are still missing, but, with the advent organs and tissues such as the brain, blood and the kidney in most of new technologies, such studies will emerge. patients, the vast majority of whom are women of childbearing age, Better understanding of the epigenome is needed to under- impels efforts to develop diagnostic tools and effective therapeu- stand how it supplements the genetic contribution to the dis- tics. The prevalence ranges from 20 to 150 cases per 100,000 peo- ease.
    [Show full text]
  • Pathophysiology of Immune Thrombocytopenic Purpura: a Bird's-Eye View
    Egypt J Pediatr Allergy Immunol 2014;12(2):49-61. Review article Pathophysiology of immune thrombocytopenic purpura: a bird's-eye view. Amira Abdel Moneam Adly Pediatrics Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt ABSTRACT and B lymphocytes (including T-helper, T- Immune thrombocytopenic purpura (ITP) is a cytotoxic, and T-regulatory lymphocytes) 6. common autoimmune disorder resulting in isolated The triggering event for ITP is unknown7, but thrombocytopenia. It is a bleeding disorder continued research is providing new insights into characterized by low platelet counts due to decreased the underlying immunopathogenic processes as well platelet production as well as increased platelet as the cellular and molecular mechanisms involved destruction by autoimmune mechanisms. ITP can in megakaryocytopoiesis and platelet turnover. present either alone (primary) or in the setting of other Although historically ITP-associated thrombo- conditions (secondary) such as infections or altered cytopenia was attributed solely to increased rates of immune states. ITP is associated with a loss of destruction of antibody- coated platelets, it has tolerance to platelet antigens and a phenotype of become evident that suboptimal platelet production accelerated platelet destruction and impaired platelet also plays a role 8. production. Although the etiology of ITP remains Bleeding is due to decreased platelet production unknown, complex dysregulation of the immune as well as accelerated platelet destruction mediated system is observed in ITP patients. Antiplatelet in part by autoantibody-based destruction antibodies mediate accelerated clearance from the mechanisms9. Most autoantibodies in ITP are circulation in large part via the reticuloendothelial isotype switched and harbor somatic mutations10, (monocytic phagocytic) system.
    [Show full text]
  • B Cell Activation and Escape of Tolerance Checkpoints: Recent Insights from Studying Autoreactive B Cells
    cells Review B Cell Activation and Escape of Tolerance Checkpoints: Recent Insights from Studying Autoreactive B Cells Carlo G. Bonasia 1 , Wayel H. Abdulahad 1,2 , Abraham Rutgers 1, Peter Heeringa 2 and Nicolaas A. Bos 1,* 1 Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, 9713 Groningen, GZ, The Netherlands; [email protected] (C.G.B.); [email protected] (W.H.A.); [email protected] (A.R.) 2 Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9713 Groningen, GZ, The Netherlands; [email protected] * Correspondence: [email protected] Abstract: Autoreactive B cells are key drivers of pathogenic processes in autoimmune diseases by the production of autoantibodies, secretion of cytokines, and presentation of autoantigens to T cells. However, the mechanisms that underlie the development of autoreactive B cells are not well understood. Here, we review recent studies leveraging novel techniques to identify and characterize (auto)antigen-specific B cells. The insights gained from such studies pertaining to the mechanisms involved in the escape of tolerance checkpoints and the activation of autoreactive B cells are discussed. Citation: Bonasia, C.G.; Abdulahad, W.H.; Rutgers, A.; Heeringa, P.; Bos, In addition, we briefly highlight potential therapeutic strategies to target and eliminate autoreactive N.A. B Cell Activation and Escape of B cells in autoimmune diseases. Tolerance Checkpoints: Recent Insights from Studying Autoreactive Keywords: autoimmune diseases; B cells; autoreactive B cells; tolerance B Cells. Cells 2021, 10, 1190. https:// doi.org/10.3390/cells10051190 Academic Editor: Juan Pablo de 1.
    [Show full text]
  • Mechanisms Governing Anaphylaxis: Inflammatory Cells, Mediators
    International Journal of Molecular Sciences Review Mechanisms Governing Anaphylaxis: Inflammatory Cells, Mediators, Endothelial Gap Junctions and Beyond Samantha Minh Thy Nguyen 1, Chase Preston Rupprecht 2, Aaisha Haque 3, Debendra Pattanaik 4, Joseph Yusin 5 and Guha Krishnaswamy 1,3,* 1 Department of Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27106, USA; [email protected] 2 The Rowan School of Osteopathic Medicine, Stratford, NJ 08084, USA; [email protected] 3 The Bill Hefner VA Medical Center, Salisbury, NC 27106, USA; [email protected] 4 Division of Allergy and Immunology, UT Memphis College of Medicine, Memphis, TN 38103, USA; [email protected] 5 The Division of Allergy and Immunology, Greater Los Angeles VA Medical Center, Los Angeles, CA 90011, USA; [email protected] * Correspondence: [email protected] Abstract: Anaphylaxis is a severe, acute, life-threatening multisystem allergic reaction resulting from the release of a plethora of mediators from mast cells culminating in serious respiratory, cardiovascular and mucocutaneous manifestations that can be fatal. Medications, foods, latex, exercise, hormones (progesterone), and clonal mast cell disorders may be responsible. More recently, novel syndromes such as delayed reactions to red meat and hereditary alpha tryptasemia have been described. Anaphylaxis manifests as sudden onset urticaria, pruritus, flushing, erythema, Citation: Nguyen, S.M.T.; Rupprecht, angioedema (lips, tongue, airways, periphery), myocardial dysfunction (hypovolemia, distributive
    [Show full text]
  • B Cell Checkpoints in Autoimmune Rheumatic Diseases
    REVIEWS B cell checkpoints in autoimmune rheumatic diseases Samuel J. S. Rubin1,2,3, Michelle S. Bloom1,2,3 and William H. Robinson1,2,3* Abstract | B cells have important functions in the pathogenesis of autoimmune diseases, including autoimmune rheumatic diseases. In addition to producing autoantibodies, B cells contribute to autoimmunity by serving as professional antigen- presenting cells (APCs), producing cytokines, and through additional mechanisms. B cell activation and effector functions are regulated by immune checkpoints, including both activating and inhibitory checkpoint receptors that contribute to the regulation of B cell tolerance, activation, antigen presentation, T cell help, class switching, antibody production and cytokine production. The various activating checkpoint receptors include B cell activating receptors that engage with cognate receptors on T cells or other cells, as well as Toll-like receptors that can provide dual stimulation to B cells via co- engagement with the B cell receptor. Furthermore, various inhibitory checkpoint receptors, including B cell inhibitory receptors, have important functions in regulating B cell development, activation and effector functions. Therapeutically targeting B cell checkpoints represents a promising strategy for the treatment of a variety of autoimmune rheumatic diseases. Antibody- dependent B cells are multifunctional lymphocytes that contribute that serve as precursors to and thereby give rise to acti- cell- mediated cytotoxicity to the pathogenesis of autoimmune diseases
    [Show full text]
  • Difference Between Hypersensitivity and Autoimmunity Key Difference – Hypersensitivity Vs Autoimmunity
    Difference Between Hypersensitivity and Autoimmunity www.differencebetwee.com Key Difference – Hypersensitivity vs Autoimmunity Autoimmunity is an adaptive immune response mounted against self-antigens. In simple terms, when your body is acting against its own cells and tissues, this is called an autoimmune reaction. An exaggerated and inappropriate immune response to an antigenic stimulus is defined as a hypersensitivity reaction. Unlike autoimmune reactions that are triggered only by the endogenous antigens, hypersensitivity reactions are triggered by both endogenous and exogenous antigens. This is the key difference between hypersensitivity and autoimmunity. What is Hypersensitivity? An exaggerated and inappropriate immune response to an antigenic stimulus is defined as a hypersensitivity reaction. The first exposure to a particular antigen activates the immune system and, antibodies are produced as a result. This is called sensitization. Subsequent exposures to the same antigen give rise to hypersensitivity. Few important facts regarding the hypersensitivity reactions are given below They can be elicited by both exogenous and endogenous agents. They are a result of an imbalance between the effector mechanisms and the countermeasures that are there to control any inappropriate execution of an immune response. The presence of a genetic susceptibility increases the likelihood of hypersensitivity reactions. The manner in which hypersensitivity reactions harm our body is similar to the way that the pathogens are destroyed by immune reactions. Figure 01: Allergy According to the Coombs and Gell classification, there are four main types of hypersensitivity reactions. Type I- Immediate Type/ Anaphylactic Mechanism Vasodilation, edema, and contraction of smooth muscles are the pathological changes that take place during the immediate phase of the reaction.
    [Show full text]
  • 2 Allergy, Immunodeficiency, Autoimmunity and COVID-19
    2 Allergy, Immunodeficiency, Autoimmunity and COVID-19 Vaccination Frequently Asked Questions (FAQ) 17 February 2021 This information has been developed by ASCIA, the peak professional body of clinical immunology/allergy specialists in Australia and New Zealand, to answer questions regarding COVID-19 vaccination in relation to allergy, immunodeficiency and autoimmunity. ASCIA will update this FAQ when new information is available. 1. Why is the COVID-19 vaccination program important? Vaccination is an important way to reduce the risk of developing infectious diseases which can easily spread. This includes COVID-19, which is caused by infection with the SARS-CoV-2 coronavirus. Immunity occurs after the vaccine stimulates a person’s immune system to make antibodies (immunoglobulins) to help protect the body from future infections. This means that if a person is vaccinated, they will be less likely to get COVID-19. Even if a person does get infected, it is likely to be a milder illness. Public health measures and restrictions that were implemented by the Australian and New Zealand governments since March 2020 have been successful in controlling the spread of COVID-19 in our countries. However, the COVID-19 pandemic has been a major cause of illness and deaths in other countries. This means that vaccination programs are required throughout the world, including Australia and New Zealand. 2. Which COVID-19 vaccines have been approved in Australia and New Zealand? Pfizer/BioNTech COMIRNATY mRNA-based COVID-19 vaccine has been provisionally approved by the Therapeutic Goods Administration (TGA), part of the Australian Government Department of Health, and by Medsafe in New Zealand for people 16 years and older.
    [Show full text]
  • Tests for Autoimmune Diseases Test Codes 249, 16814, 19946
    Tests for Autoimmune Diseases Test Codes 249, 16814, 19946 Frequently Asked Questions Panel components may be ordered separately. Please see the Quest Diagnostics Test Center for ordering information. 1. Q: What are autoimmune diseases? A: “Autoimmune disease” refers to a diverse group of disorders that involve almost every one of the body’s organs and systems. It encompasses diseases of the nervous, gastrointestinal, and endocrine systems, as well as skin and other connective tissues, eyes, blood, and blood vessels. In all of these autoimmune diseases, the underlying problem is “autoimmunity”—the body’s immune system becomes misdirected and attacks the very organs it was designed to protect. 2. Q: Why are autoimmune diseases challenging to diagnose? A: Diagnosis is challenging for several reasons: 1. Patients initially present with nonspecific symptoms such as fatigue, joint and muscle pain, fever, and/or weight change. 2. Symptoms often flare and remit. 3. Patients frequently have more than 1 autoimmune disease. According to a survey by the Autoimmune Diseases Association, it takes up to 4.6 years and nearly 5 doctors for a patient to receive a proper autoimmune disease diagnosis.1 3. Q: How common are autoimmune diseases? A: At least 30 million Americans suffer from 1 or more of the 80 plus autoimmune diseases. On average, autoimmune diseases strike three times more women than men. Certain ones have an even higher female:male ratio. Autoimmune diseases are one of the top 10 leading causes of death among women age 65 and under2 and represent the fourth-largest cause of disability among women in the United States.3 Women’s enhanced immune system increases resistance to infection, but also puts them at greater risk of developing autoimmune disease than men.
    [Show full text]
  • Espaci 55A a 313 316 a 314 a 317 A
    ESPACI 55A A 313 316 AUTOIMMUNITY AND PRIMARY IMMUNE DEFICIENCIES (PID) RESPIRATORY SYMPTOMS AND ATOPIC SENSITIZATION AMONG ESTONIAP; 10-12 YEARS OLD CHILDREN. Lina Gomez & Mikhail N.Yartsev Childhood Unit, Institute of Immunology. Moscow I;. Julpc, M. Vasar, M.-A. Riikjant, L. Braback, A. hutsson, B. BjorkstCn A total of 172 autoimmune disorders was recorded in 262 children with Tartu University Children's Hospital (K.J., M.V.), Tallinn Children's Hospital (M.- some lnajor PID (hypogammaglobulinemia (X-linked, with hyper-lgM. A.R.) Estonia; Sundsvall Hospital (L.B.), Department of Occupational Health, Sundsvall (A.K.), Linkoping Univcrsit) (B.B.) Swcdcn. common variable). IgA-deficiency, chronic mucocutaneous candidosis (CMCC) and Wiskott-Aldrich syndrome), while no autoimmunity was For establishing asthma prcvalcncc among Estonian schoolchildrcn 753 10-12 years manifest in 103 patients with several other PID (ataxia-telangiectasia. old childrcn in Tallinn (Tln) and 766 in Tmu (Ta) were invcstigatcd in a cross- sectional study, including parental questionnaires, skin prick tcsts (SPT), scrial PEF- clironic granulomatous disease, hyper-lgE syndrome). Rheumatoid-like measurements and provocation tcsts with mctacholinc and cxcrcisc tcsts. arthritis (29%) and granulocytopenia (23%) were typical features of Allergic rcspiratory symptoms were less common anlong Estonian childrcn than hypogammaglobul~nemic states and often responded to pathogenebc among childrcn in West- and North-European countries. 5.1% of childrcn in Tln therapy. Autoimmune endocrinopathy developed in most patients with and 4.1% in Ta had nocturnal cough without signs of cold; 9.4% of childrcn in Tln and 5.8 in Ta had whcczing in thc chest during cold, physical cxcrtion or in contact CPACC (70%).
    [Show full text]
  • Autoimmune Diseases
    POLICY BRIEFING Autoimmunity March 2016 of this damage the adrenal gland does not produce enough steroid hormones (primary adrenal insufficiency), resulting Key points in symptoms which include fatigue, muscle weakness, and a loss of appetite. This can be fatal if not recognised and • Autoimmunity involves a misdirection of the body’s treated, but treatment is relatively simple. immune system against its own tissues, causing a large • Grave’s disease – affecting the thyroid, Grave’s disease is number of diseases. one of the most common causes of hyperthyroidism. It • More than 80 autoimmune diseases have so far been results from the production of antibodies that mimic Thyroid identified: some affect only one tissue or organ, while Stimulating Hormone, which produces a false signal causing others are ‘systemic’ (affection multiple sites of the the thyroid gland to produce excessive thyroid hormone. body). Symptoms including insomnia, tremor, and hyperactivity. • Hundreds of thousands of individuals in the UK are • Type 1 diabetes – diabetes mellitus type 1 is a consequence of affected by autoimmunity. the autoimmune destruction of cells in the pancreas which • Most autoimmune diseases have very long-term effects produce insulin. Insulin is essential to control blood sugar on health, placing a large burden on the NHS and on levels and if left uncontrolled the disease can lead to serious national economies. complications, such as damage to the nerves, heart disease, • Current treatment aims to minimise symptoms and is and problems with the retina. Without adequate treatment often not curative. It is imperative that immunological type 1 diabetes would be fatal. research receives adequate investment in order to better • Crohn’s disease – a type of inflammatory bowel disease (IBD), understand these conditions so that we can open up new Crohn’s is a result of chronic inflammation of the lining of the therapeutic strategies.
    [Show full text]
  • Human Autoimmunity and Associated Diseases
    Human Autoimmunity and Associated Diseases Human Autoimmunity and Associated Diseases Edited by Kenan Demir and Selim Görgün Human Autoimmunity and Associated Diseases Edited by Kenan Demir and Selim Görgün This book first published 2021 Cambridge Scholars Publishing Lady Stephenson Library, Newcastle upon Tyne, NE6 2PA, UK British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library Copyright © 2021 by Kenan Demir and Selim Görgün and contributors All rights for this book reserved. No part of this book may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission of the copyright owner. ISBN (10): 1-5275-6910-1 ISBN (13): 978-1-5275-6910-2 TABLE OF CONTENTS Preface ...................................................................................................... viii Chapter One ................................................................................................. 1 Introduction to the Immune System Kemal Bilgin Chapter Two .............................................................................................. 10 Immune System Embryology Rümeysa Göç Chapter Three ............................................................................................. 18 Immune System Histology Filiz Yılmaz Chapter Four .............................................................................................. 36 Tolerance Mechanisms and Autoimmunity
    [Show full text]